Objective To determine the effect of ropivacaine on peripheral neuropathy in diabetic rats and its possible mechanism.Methods Forty-eight Sprague–Dawley rats were randomly divided into six groups: nondiabetic control group, nondiabetic group A (0.25% ropivacaine), nondiabetic group B (0.75% ropivacaine), diabetic control group (diabetic peripheral neuropathy (DPN) +artificial cerebrospinal fluid), diabetic group A (DPN+0.25% ropivacaine), and diabetic group B (DPN + 0.75% ropivacaine), with eight rats in each group. Within an hour of the last administration, the sciatic motor nerve conduction velocity (MNCV) of each group was measured, and the morphological changes of rat sciatic nerve were observed by HE, Weil’s staining and electron microscopy. The expression of transient receptor potential vanilloid (TRPV1) in the spinal cord dorsal horn of rats was analyzed by immunohistochemistry, and the expression of Calcitonin gene-related peptide (CGRP) protein in the spinal cord was analyzed by Western blot.Results Compared with the nondiabetic control group, elevated blood glucose, decreased weight and reduced average mechanical withdrawal threshold (MWT), additionally, the sciatic nerves showed significantly slowed conduction velocity (both P<0.001) and damaged pathological structure, the expression of TRPV1 and CGRP were decreased (both P<0.001) in the diabetic groups. Compared with the diabetic control group, down-regulation of TRPV1 and CGRP in spinal cord was significant for the diabetic groups A and B treated with 0.25 and 0.75% ropivacaine, the higher concentration of ropivacaine correlated with a greater change.Conclusion Ropivacaine can significantly block sciatic nerve conduction velocity in DPN rats in a concentration-dependent manner, which may be related to the expression of the TRPV1-CGRP pathway.

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based fusion protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were downregulated after 24 h incubation with VHH-0031 in a dose-dependent manner. In vivo , VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared with the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients.

The currently used anti-cytokine therapeutic antibodies cannot selectively neutralize pathogenic cytokine signalling that cause collateral damage to protective signalling cascades. The single domain chain firstly discovered in Camelidae displays fully functional ability in antigen-binding against variable targets, which has been seemed as attractive candidates for the next-generation biologic drug study. In this study, we established a simple prokaryotic expression system for a dual target-directed single domain-based Fusion Protein against the interleukin-6 receptor and human serum, albumin, the recombinant anti-IL-6R fusion protein (VHH-0031). VHH-0031 exhibited potent anti-inflammatory effects produced by LPS on cell RAW264.7, where the major cytokines and NO production were down-regulated after 24 hr incubation with VHH-0031 in a dose-dependent manner. In vivo, VHH-0031 presented significant effects on the degree reduction of joint swelling in the adjuvant-induced arthritis (AIA) rat, having a healthier appearance compared to the dexamethasone. The expression level of JNK protein in the VHH-0031 group was significantly decreased, demonstrating that VHH-0031 provides a low-cost and desirable effect in the treatment of more widely patients.

Context: It is urgent to develop drugs with independent intellectual property rights and more reasonable price, safe and effective treatment of RA.Objective: To study the inhibitory effect of curcumin derivative FM0807 on the proliferation of RA-FLS cells and its possible mechanism.Materials&Methods: Rheumatiod arthritis fibroblast-like synoviocyte (RA-FLS) were cultured in alone or in the presence of FM0807 (25μM, 50μM and 100μM). MTT method was used to analyze the effect of cell proliferation, Hoechst 33342/PI staining was used to observe the effect of apoptosis. Cell migration assay was used to observe the effect of migration ability of RA-FLS. The expression of JAK2,STAT3, IL-6 and IL-1β gene was determined by RT-PCR method. Western blotting assay was used to detect the expression of JAK2-STAT3 signaling pathway related proteins.Results: A 72-hour exposure FM0807 result in cell proliferation inhibition significantly(IC50=41.38μM). The migration of RA-FLS is inhibited by FM0807 100µM in 72 h (P<0 05). High Content Screening showed that the apoptosis rate of RA-FLS was up regulated after treated FM0807. Presence of FM0807 in the culture medium strongly inhibited JAK2,STAT3,IL-6 and IL-1βmRNA expression in a concentration-dependent manner. Western blot demonstrated a substantially reduced protein expression of phosphorylation of JAK2 and STAT3. At the same time, the anti-apoptotic protein Bcl-2 and the key proteins of PI3K cell pathway including Akt and mTOR were down-regulated. on the contrary, the expression of apoptosis execution protein Cleaved-caspase3 and Bax were up-regulated.Conclusion: Curcumin derivative FM0807 may inhibit the proliferation of RA-FLS and promote its apoptosis by inhibiting JAK2-STAT3 signaling pathway.